“A consensus statement from the American Diabetes Association and the European Association for the Study of Diabetes recommends metformin therapy as first-line therapy along with lifestyle modification to treat type 2 diabetes mellitus.” Philbrick, Am. J. Health Syst. Pharm., 2009 Nov. 15; 66 (22):2017-23. According to Wikipedia, metformin was introduced to the United Kingdom in 1958, Canada in 1972, and the United States in 1995. Metformin is now believed to be the most widely prescribed anti-diabetic drug in the world. In the United States alone, more than 40 million prescriptions were filled in 2008 for its generic formulations. Because of metformin's status as a first line diabetic therapy, Bristol-Myers Squibb's diabetic drug Glucophage® brought in peak sales of $1.7 billion before its patent expired in 2000.
Metformin is a synthetic biguanadine having a molecular weight of about 165. Its molecular structure is shown in FIG. 1a. 
It is believed that metformin improves glucose control in diabetics by increasing AMPK in hepatocytes, thereby providing control over glucose production.
Despite the effectiveness of metformin as a diabetes medication, it nonetheless suffers from some drawbacks. In particular, Marathe, Br. J. Clin., Pharmacol., 50, 325-332 (2000) has reported that, while metformin is effectively taken up in the small intestine, it is poorly absorbed in the colon. As a result, the time window for effective plasma concentrations of metformin is limited to about 6 hours. See, for example, FIG. 4 of US Patent Publication 2007-0154548 (Cheng Xiu), which reports that the window in which metformin is above ½ of its Cmax is only about 6 hours. Because of this narrow absorption window, metformin is typically presecribed to be taken about 2-3 times a day.
A number of attempts at improving the bioavailability of metformin involve providing metformin in an extended release dosage form that releases metformin in the colon. See, for example, US Patent Publication 2007275061; US Patent Publication 2007264331; and US Patent Publication 2009124702. However, these efforts to not improve the uptake efficiency of metformin in the colon.
Other attempts at improving the bioavailability of metformin involve providing metformin salts of lipophilic acids. See, for example, US Patent Publication 2003-0220301 (Lal).
US Patent Publication 2005-0158374 (Wong) discloses a complex comprised of metformin and a transport moiety, such as a fatty acid, is described. Wong reports that this complex has an enhanced absorption in the gastrointestinal tract, particularly the lower gastrointestinal tract. The complex, and compositions and dosage forms prepared using the complex, provide for absorption by the body of the drug through a period of ten to twenty-four hours, thus enabling a once-daily dosage form for metformin.
Other attempts have been made to improve the bioavailability of metformin by delivering it as a more lipophilic prodrug. In particular, the investigators in Huttunen, J. Med. Chem., 2009, 52, 14, 4142-4148 noted that N—S bonds may be cleaved by endogenous thiols and created sulfonamide prodrugs of metformin (FIG. 1c). The investigators report that the enhanced lipophilicity of these prodrugs appear to allow their passive diffusion into intestinal cells and that the metformin bioavailability increased from about 43% to about 60%.